5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Malignant Tumor

NCT ID: NCT02632370

Last Updated: 2019-02-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 69 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2018-12-31

Brief Summary

In support of the US marketing application for 5-ALA, this single arm trial is being conducted to establish the efficacy and safety of Gliolan® (5-ALA) in patients with newly diagnosed or recurrent malignant gliomas. The hypothesis of the study is Gliolan® (5-ALA), as an adjunct to tumor resection, is safe and that real-time tissue fluorescence correlates with malignant histopathology. The primary objective in this single arm study is to define the positive predictive value (PPV) of Gliolan®-induced PPIX fluorescence for malignant tumor at the time of initial resection and first use of FGS by taking a biopsy of tissue presenting with red fluorescence when observed during the course of resection of new or recurrent malignant gliomas. The functionality and performance reliability of the blue light excitation microscope platforms will be assessed.

Detailed Description

Primary Objectives

• To determine whether Gliolan® (5-ALA)-induced PPIX fluorescence correlates with malignant tumor histopathology (in a minimum of 3-5 serial biopsies taken from the red fluorescent region of tissue resection).
• To determine the patient safety profile of both oral Gliolan® (5-ALA), as well as use of the fluorescence operative microscope. These will include use of commonly accepted toxicity measures as well as recording surgically-related neurological deficits within the six weeks after surgery.
• To determine functionality and performance reliability of the blue light excitation microscope platforms (Zeiss Pentero, Leica OH4, Leica OH6 and others).

Secondary Objectives

• To correlate PPIX-containing extracellular microvesicles recovered from blood (at multiple time points prior to and following tumor resection) with the pre-operative MRI tumor volume.
• To characterize the presence and longitudinal changes in microvesicle biomarkers recovered from blood evaluating EGFRvIII, IDH1/2 wt and mutations and others. These microvesicular blood genes will be identified and correlated with the same microvesicular genes identified in tissue at the time of surgery.

Conditions

Malignant Gliomas

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Gliolan®

Gliolan® is presented as a powder for oral solution in 60 ml colorless glass vials. The formulation contains 1.5 g 5-aminolevulinic acid hydrochloride corresponding to 1.17 g of 5-aminolevulinic acid. The oral solution is intended for single (partial) use.

Gliolan®

Intervention Type: DRUG

single dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively

Fluorescence-Guided Surgery

Intervention Type: PROCEDURE

performed utilizing blue light. At least 3-5 fluorescent tissue samples will be taken.

Interventions

Gliolan®

single dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively

Intervention Type: DRUG

Fluorescence-Guided Surgery

performed utilizing blue light. At least 3-5 fluorescent tissue samples will be taken.

Intervention Type: PROCEDURE

Other Intervention Names

5-ALA; FGS

Eligibility Criteria

Inclusion Criteria

• Subjects included must have an MRI documenting a primary brain tumor for which resection is indicated and has been planned. These patients will include those with newly diagnosed or recurrent malignant gliomas. Standard criteria for diagnosis will include a distinct ring-like pattern of contrast enhancement with thick irregular walls on MRI for patients with a presumed newly diagnosed malignant glioma.
• Age 18-80.
• Karnofsky>60%.
• Subjects must have normal organ and marrow function as defined below:

Leukocytes >3,000/mL Platelets >100,000/mL Total bilirubin below upper limit of normal AST (SGOT)/ALT (SGPT) <2.5 X institutional upper limit of normal Creatinine below upper limit of normal OR Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Exclusion Criteria

• Ability to understand and the willingness to sign a written informed consent document. Translation will be provided as appropriate by institution.
• Inclusion of Women and Minorities: Both men and women and members of all ethnic groups are eligible for this trial.

• Patients with radiographic tumors of, or involving, nonresectable midline, the basal ganglia, or brain stem as assessed by MRI.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA). Patients should refrain from use of other potential phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts) for 72 h.
• Personal or family history of porphyria.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. . Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 5-aminolevulinic acid (5-ALA), breastfeeding should be discontinued if the mother is treated with 5-aminolevulinic acid (5-ALA).
• Women who are pregnant will be excluded from the trial as aminolevulinic acid (ALA) is unknown to be teratogenic or have abortifacient effects Prior history of GI perforation, diverticulitis, and/or peptic ulcer disease.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Constantinos Hadjipanayis

OTHER

Sponsor Role: lead

Responsible Party

Constantinos Hadjipanayis

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Bob Carter, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

George Washington University

Washington D.C., District of Columbia, United States

Delray Medical Center

Delray Beach, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

CentraCare St. Cloud Hospital

Saint Cloud, Minnesota, United States

St. Luke's Marion Bloch Neuroscience Institute

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of New Mexico School of Medicine, Department of Neurosurgery

Albuquerque, New Mexico, United States

Mount Sinai Beth Israel

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

Penn State- Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

CGH932015

Identifier Type: OTHER

Identifier Source: secondary_id

PRMC 15-085

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 15-2034-0001

Identifier Type: -

Identifier Source: org_study_id